Alterations by perfluorooctanoic acid of glycerolipid metabolism in rat liver.

The effects of perfluorooctanoic acid (PFOA) feeding on hepatic levels of glycerolipids and the underlying mechanism were investigated. Feeding of rats with 0.01% of PFOA in the diet for 1 week caused an increase in the contents of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) and triglyceride (TG), which were 2.2, 2.4, 2.4, 1.6 and 5.2 times over control, respectively, on the basis of whole liver. The activities of glycerol-3-phosphate acyltransferase, diacylglycerol kinase and PtdSer decarboxylase were significantly increased upon PFOA feeding, whereas the activities of CTP:phosphoethanolamine cytidylyltransferase and PtdEtn N-methyltransferase were decreased. On the other hand, the activity of CTP:phosphocholine cytidylyltransferase was not increased by PFOA. Upon PFOA feeding, hepatic level of 16:0-18:1 PtdCho was markedly increased and, by contrast, the levels of molecular species of PtdCho which contain 18:2 were decreased, resulting in the reduced concentration of molecular species of serum PtdCho containing 18:2. The increase in the level of hepatic 16:0-18:1 PtdCho seemed to be due to 3-fold increase in the activities of both delta9 desaturase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase. The mechanism by which PFOA causes the accumulation of glycerolipids in liver was discussed.

[1]  R. Sundler Ethanolaminephosphate cytidylyltransferase. Purification and characterization of the enzyme from rat liver. , 1975, The Journal of biological chemistry.

[2]  Y Cai,et al.  Thyromimetic action of the peroxisome proliferators clofibrate, perfluorooctanoic acid, and acetylsalicylic acid includes changes in mRNA levels for certain genes involved in mitochondrial biogenesis. , 1996, Archives of biochemistry and biophysics.

[3]  H. Okuyama,et al.  Selectivity of diacylglycerophosphate synthesis in subcellular fractions of rat liver. , 1978, Archives of biochemistry and biophysics.

[4]  J. Vance Compartmentalization of phospholipids for lipoprotein assembly on the basis of molecular species and biosynthetic origin. , 1988, Biochimica et biophysica acta.

[5]  O. Spydevold,et al.  The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. , 1992, Biochimica et biophysica acta.

[6]  M. Geelen,et al.  Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. , 1989, Biochimica et biophysica acta.

[7]  N. Oshino,et al.  Stimulation by phenols of the reoxidation microsomal bound cytochrome b5 and its implication to fatty acid desaturation. , 1971, Journal of biochemistry.

[8]  K P Lee,et al.  Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. , 1987, Experimental and molecular pathology.

[9]  R. Bell,et al.  A highly sensitive assay for microsomal diacyglycerol acyltransferase activity from isolated fat cells. , 1976, Analytical biochemistry.

[10]  N. Kudo,et al.  Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. , 1997, Toxicology and applied pharmacology.

[11]  I. Kozo,et al.  Alteration in enzyme activities of de novo phosphatidylcholine biosynthesis in rat liver by treatment with typical inducers of microsomal drug-metabolizing system. , 1980 .

[12]  C. Kent,et al.  Eukaryotic phospholipid biosynthesis. , 1995, Annual review of biochemistry.

[13]  Y. Kawashima,et al.  Reduction by clofibric acid of serum arachidonic acid in rats. Effect on the acyl composition of renal phospholipids. , 1992, Biochemical pharmacology.

[14]  Y. Kawashima,et al.  Selective increase in acylation of 1-acylglycerophosphorylcholine in livers of rats and mice by peroxisome proliferators. , 1984, Biochimica et biophysica acta.

[15]  D. Vance,et al.  The role of phosphatidylcholine biosynthesis in the secretion of lipoproteins from hepatocytes. , 1985, Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire.

[16]  Y. Kawashima,et al.  Modulation by dietary oils and clofibric acid of arachidonic acid content in phosphatidylcholine in liver and kidney of rat: effects on prostaglandin formation in kidney. , 1994, Biochimica et biophysica acta.

[17]  R. Sundler,et al.  Regulation of phospholipid biosynthesis in isolated rat hepatocytes. Effect of different substrates. , 1975, The Journal of biological chemistry.

[18]  N. Reo,et al.  Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver. , 1996, Toxicology letters.

[19]  Y. Kawashima,et al.  Characterization of hepatic responses of rat to administration of perfluorooctanoic and perfluorodecanoic acids at low levels. , 1995, Toxicology.

[20]  K. Gorgas,et al.  Biochemical effects and zonal heterogeneity of peroxisome proliferation induced by perfluorocarboxylic acids in rat liver , 1989, Hepatology.

[21]  F. Snyder,et al.  Novel quantitative method for determination of molecular species of phospholipids and diglycerides. , 1984, Journal of chromatography.

[22]  Phosphatidylethanolamine metabolism in rat liver after partial hepatectomy. Control of biosynthesis of phosphatidylethanolamine by the availability of ethanolamine. , 1992, The Biochemical journal.

[23]  M Tanaka,et al.  The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids. , 1985, Journal of biochemistry.

[24]  D. Vance,et al.  Pitfalls and problems in studies on the methylation of phosphatidylethanolamine. , 1983, The Journal of biological chemistry.

[25]  D. Vance,et al.  Fatty acids promote translocation of CTP:phosphocholine cytidylyltransferase to the endoplasmic reticulum and stimulate rat hepatic phosphatidylcholine synthesis. , 1983, The Journal of biological chemistry.

[26]  Y. Kawashima,et al.  The mechanism for the increased supply of phosphatidylcholine for the proliferation of biological membranes by clofibric acid, a peroxisome proliferator. , 1994, Biochimica et biophysica acta.

[27]  F. Snyder,et al.  Tumor lipids: metabolic relationships derived from structural analyses of acyl, alkyl, and alk-l-enyl moieties of neutral glycerides and phosphoglycerides. , 1969, Archives of biochemistry and biophysics.

[28]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[29]  P. Weinhold,et al.  The stimulation and binding of CTP: phosphorylcholine cytidylyltransferase by phosphatidylcholine-oleic acid vesicles. , 1985, Biochimica et biophysica acta.

[30]  Y. Kawashima,et al.  Sex-related differences in the enhancing effects of perfluoro-octanoic acid on stearoyl-CoA desaturase and its influence on the acyl composition of phospholipid in rat liver. Comparison with clofibric acid and tiadenol. , 1989, The Biochemical journal.

[31]  M E Andersen,et al.  Pathological and hepatic ultrastructural effects of a single dose of perfluoro-n-decanoic acid in the rat, hamster, mouse, and guinea pig. , 1987, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[32]  M E Hurtt,et al.  Effects of ammonium perfluorooctanoate on Leydig cell function: in vitro, in vivo, and ex vivo studies. , 1995, Toxicology and applied pharmacology.

[33]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[34]  J. Vance The use of newly synthesized phospholipids for assembly into secreted hepatic lipoproteins. , 1989, Biochimica et biophysica acta.

[35]  N. Reo,et al.  Effects of peroxisome proliferators on rat liver phospholipids: sphingomyelin degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid. , 1998, Chemical research in toxicology.